The fine specificity of mannose-binding and galactose-binding lectins revealed using outlier motif analysis of glycan array data
The fine specificity of mannose-binding and galactose-binding lectins revealed using outlier motif analysis of glycan array data
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DOI：
10.1093/glycob/cwr128
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发表时间：
2012-01-01
期刊：
影响因子：
4.3
通讯作者：
Haab, Brian B.
中科院分区：
文献类型：
--
作者：
Maupin, Kevin A.;Liden, Daniel;Haab, Brian B.
聚糖结合蛋白通常用作分析试剂来检测生物样品中特定聚糖结构的水平。为了正确解释其结合数据，需要详细了解聚糖结合蛋白的特异性。聚糖阵列是表征聚糖结合特异性的一项强大技术。然而，由于某些聚糖结合蛋白的复杂精细特异性，聚糖阵列数据的解释可能很困难。我们开发了一种称为异常基序分析的系统方法，用于从聚糖阵列数据中提取精细特异性信息，并将该方法应用于四种常用凝集素的研究：两种甘露糖结合剂（伴刀豆球蛋白 A 和 Lens culinaris）和两种半乳糖结合剂（紫荆花和花生凝集素）。该研究证实了每种凝集素已知的主要特异性，并揭示了对其结合偏好的新见解。 Lens culinaris 的主要特异性可能是非末端、α 连接的甘露糖，其 2' 碳上有一个单键，这比以前的定义受到更多限制。我们发现紫紫荆 (BPL) 的特异性比之前报道的更广泛，表明 BPL 在某些限制下可以结合末端 N-乙酰半乳糖胺 (GalNAc) 和倒数第二个 β 连接半乳糖。除了末端 Gal beta 1,3GalNAc（一种常见的 O 连接糖蛋白基序）之外，花生凝集素还可以结合末端 Gal beta 1,3Gal（一种糖脂基序）。这些结果可用于更准确地解释使用这些经过充分研究的凝集素获得的数据。此外，这项研究展示了一种从聚糖阵列数据中提取精细特异性信息的系统且通用的方法。
Glycan-binding proteins are commonly used as analytical reagents to detect the levels of specific glycan structures in biological samples. A detailed knowledge of the specificities of glycan-binding proteins is required for properly interpreting their binding data. A powerful technology for characterizing glycan-binding specificity is the glycan array. However, the interpretation of glycan-array data can be difficult due to the complex fine specificities of certain glycan-binding proteins. We developed a systematic approach, called outlier-motif analysis, for extracting fine-specificity information from glycan-array data, and we applied the method to the study of four commonly used lectins: two mannose binders (concanavalin A and Lens culinaris) and two galactose binders (Bauhinia purpurea and peanut agglutinin). The study confirmed the known, primary specificity of each lectin and also revealed new insights into their binding preferences. Lens culinaris's main specificity may be non-terminal, alpha-linked mannose with a single linkage at its 2' carbon, which is more restricted than previous definitions. We found broader specificity for bauhinea purpurea (BPL) than previously reported, showing that BPL can bind terminal N-acetylgalactosamine (GalNAc) and penultimate beta-linked galactose under certain limitations. Peanut agglutinin may bind terminal Gal beta 1,3Gal, a glycolipid motif, in addition to terminal Gal beta 1,3GalNAc, a common O-linked glycoprotein motif. These results could be used to more accurately interpret data obtained using these well-studied lectins. Furthermore, this study demonstrates a systematic and general approach for extracting fine-specificity information from glycan-array data.